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Increased prognostic value of clinical–reproductive model in Chinese female patients with esophageal squamous cell carcinoma

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World Journal of Gastroenterology 2022年第13期28卷 1347-1361页

作者： Dong-Yun zhang jian-wei Ku Xue-Ke Zhao Hai-yan zhang Xin Song Hong-Fang wu Zong-min Fan Rui-Hua Xu Duo You Ran Wang Ruo-Xi Zhou Li-Dong Wang State Key Laboratory of Esophageal Cancer Prevention&Treatment and Henan Key Laboratory for Esophageal Cancer Research of the First affiliated hospital Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina department of Pathology Nanyang Medical CollegeNanyang 473061Henan ProvinceChina department of Endoscopy The Third Affiliated HospitalNanyang Medical CollegeNanyang 473061Henan ProvinceChina department of Pathology The First Affiliated HospitalNanyang Medical CollegeNanyang 473061Henan ProvinceChina department of Medical Oncology Affiliated Cancer Hospital of Zhengzhou UniversityHenan Cancer HospitalZhengzhou 450052Henan ProvinceChina department of Biology University of RichmondRichmondVA 23173United States

BACKGROUnd In China,it has been well recognized that some female patients with esophageal squamous cell carcinoma(ESCC)have different overall survival(OS)time,even with the same tumor-node-metastasis(TNM)stage,challenging the prognostic value of the TNM system *** effective predictive model is needed to accurately evaluate the prognosis of female ESCC *** To construct a novel prognostic model with clinical and reproductive data for Chinese female patients with ESCC,and to assess the incremental prognostic value of the full model compared with the clinical model and TNM *** A new prognostic nomogram incorporating clinical and reproductive features was constructed based on univariatie and Cox proportional hazards survival analysis from a training cohort(n=175).The results were recognized using the internal(n=111)and independent external(n=85)validation *** capability of the clinical–reproductive model was evaluated by Harrell’s concordance index(C-index),Kaplan–Meier curve,time-dependent receiver operating characteristic(ROC),calibration curve and decision curve *** correlations between estrogen response and immune-related pathways and some gene markers of immune cells were analyzed using the TIMER 2.0 *** A clinical–reproductive model including incidence area,age,tumor differentiation,lymph node metastasis(N)stage,estrogen receptor alpha(ESR1)and beta(ESR2)expression,menopausal age,and pregnancy number was constructed to predict OS in female ESCC *** to the clinical model and TNM stage,the time-dependent ROC and C-index of the clinical–reproductive model showed a good discriminative ability for predicting 1-,3-,and 5-years OS in the primary training,internal and external validation *** on the optimal cut-off value of total prognostic scores,patients were classified into high-and low-risk groups with significantly different *** estrogen response was significantly associated with p53 and apop

关键词： Esophageal squamous cell carcinoma Female Nomogram Prognosis Estrogen receptor

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Transcatheter arterial chemoembolization after percutaneous microwave ablation and portal vein embolization for advanced hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2023年第2期22卷 213-216页

作者： jian cheng De-Fei Hong cheng-wu zhang Xiao-ming Fan Zu-yan Luo wei-Feng Yao Li-ming Jin General Surgery Cancer CenterDepartment of Hepatobiliary&Pancreatic Surgery and Minimally Invasive SurgeryZhejiang Provincial People’s HospitalAffiliated People’s Hospital of Hangzhou Medical CollegeHangzhou 310014China department of General Surgery Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310020China

To the Editor: Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS) promotes the future liver remnant(FLR) rapid proliferation in the short term, which in turn provides an opportunity for... 详细信息

关键词： hepatocellular liver microwave

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Clinical trial with traditional Chinese medicine intervention ''tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment'' for chronic hepatitis B-associated liver failure

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World Journal of Gastroenterology 2014年第48期20卷 18458-18465页

作者： Han-min Li Zhi-Hua Ye Jun zhang Xiang Gao yan-ming chen Xin Yao jian-Xun Gu Lei Zhan yang Ji jian-Liang Xu Ying-He Zeng Fan yang Lin Xiao guo-Guang Sheng wei Xin Qi Long Qing-Jing Zhu Zhao-Hong Shi Lian-guo Ruan Jia-Yao yang Chang-Chun Li Hong-Bin wu Sheng-Duo chen Xin-La Luo Hepatopathy Institute Affiliated Hospital of Hubei University of Chinese Medicine Hubei university of Chinese medicine Jingzhou hospital of Traditional Chinese medicine Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency School of Pharmaceutical Science and Technology Tianjin University

AIM:To study the clinical efficacy of traditional Chinese medicine(TCM)intervention"tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment"("TTK")for treating liver failure due to chronic hepatitis ***:We designed the study as a randomized controlled clinical *** number of Chinese Clinical Trial Registry is Chi CTR-TRC-12002961.A total of 144 patients with liver failure due to infection with chronic hepatitis B virus were enrolled in this randomized controlled clinical *** were randomly assigned to the following three groups:(1)a modern medicine control group(MMC group,36patients);(2)a"tonifying qi and detoxification"("TQD")group(72 patients);and(3)a"tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment"("TTK")group(36patients).Patients in the MMC group received general internal medicine treatment;patients in the"TQD"group were given a TCM formula"tonifying qi and detoxification"and general internal medicine treatment;patients in the"TTK"group were given a TCM formula of"TTK"and general internal medicine *** participants were treated for 8 wk and then followed at 48 wk following their final *** primaryefficacy end point was the patient fatality rate in each *** of various virological and biochemical indicators served as secondary *** one-way analysis of variance and the t-test were used to compare patient outcomes in the different treatment ***:At the 48-wk post-treatment time point,the patient fatality rates in the MMC,"TQD",and"TTK"groups were 51.61%,35.38%,and 16.67%,respectively,and the differences between groups were statistically significant(P0.05).Patients in the"TTK"group had significantly higher levels of serum to

关键词： Clinical study 'Tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment'('TTK') Liver regeneration Treatment with integrated traditional and Western medicine Chronic hepatitis B-associated liver failure

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A ribosomal gene panel predicting a novel synthetic lethality in non-BRCAness tumors

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Signal Transduction and Targeted Therapy 2023年第6期8卷 3070-3086页

作者： Chao zhang Qiang guo Lifeng chen Zheming wu Xiao-jian yan chengyang Zou Qiuxue zhang Jiahong Tan Tian Fang qunxian Rao yang Li Shizhen Shen min Deng Liewei Wang Huanyao Gao Jia Yu Hu Li cheng zhang Somaira Nowsheen Jake Kloeber Fei Zhao Ping Yin Chunbo Teng Zhongqiu Lin Kun Song Shuzhong Yao Liangqing Yao Lingying wu Yong zhang Xiaodong cheng Qinglei Gao jian Yuan Zhenkun Lou Jin-San zhang Beijing Institute of Basic Medical Sciences 100850BeijingChina department of Oncology Mayo ClinicRochesterMN55905USA school of Pharmaceutical Sciences Wenzhou Medical University325035WenzhouZhejiangChina Key Laboratory of Endocrine Gland Diseases of zhejiang Province Zhejiang Provincial People’s Hospital310014HangzhouZhejiangChina department of Gynecology Zhejiang Provincial People’s Hospital310014HangzhouZhejiangChina department of Gynecology the First Affiliated Hospital of Wenzhou Medical University325000WenzhouZhejiangChina wuhan Kingwise Biotechnology Co. Ltd.430206WuhanHubeiChina Cancer Biology Research Center(Key Laboratory of the ministry of Education) Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology430030WuhanHubeiChina department of Gynecological Oncology Sun Yat-sen Memorial HospitalSun Yat-sen University510120GuangzhouGuangdongChina zhejiang Provincial Key Laboratory of Traditional Chinese medicine for Reproductive Health Research 310006HangzhouZhejiangChina zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases 310006HangzhouZhejiangChina department of Molecular Pharmacology and Experimental Therapeutics Mayo ClinicRochesterMN55905USA department of Dermatology University of California San DiegoSan DiegoCA92122USA Key Laboratory of Saline-alkali Vegetation Ecology Restoration Ministry of EducationCollege of Life ScienceNortheast Forestry University150040HarbinChina Division of Gynecology Oncology Department of Obstetrics and GynecologyQilu HospitalShandong University250012JinanShandongChina department of Obstetrics and Gynecology the First Affiliated HospitalSun Yat-Sen University510080GuangzhouGuangdongChina department of Gynecologic Oncology Obstetrics and Gynecology Hospital of Fudan University200090ShanghaiChina department of Gynecologic Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of

Poly(ADP-ribose)polymerase(PARP)inhibitors are one of the most exciting classes of targeted therapy agents for cancers with homologous recombination(HR)***,many patients without apparent HR defects also respond well to PARP inhibitors/*** biomarker responsible for this mechanism remains ***,we identified a set of ribosomal genes that predict response to PARP inhibitors/cisplatin in HR-proficient *** inhibitor/cisplatin selectively eliminates cells with high expression of the eight genes in the identified panel via DNA damage(ATM)signaling-induced pro-apoptotic ribosomal stress,which along with ATM signaling-induced pro-survival HR repair constitutes a new model to balance the cell fate in response to DNA ***,the combined examination of the gene panel along with HR status would allow for more precise predictions of clinical response to PARP inhibitor/*** gene panel as an independent biomarker was validated by multiple published clinical datasets,as well as by an ovarian cancer organoids library we *** importantly,its predictive value was further verified in a cohort of PARP inhibitor-treated ovarian cancer patients with both RNA-seq and WGS ***,we identified several marketed drugs capable of upregulating the expression of the genes in the panel without causing HR deficiency in PARP inhibitor/cisplatin-resistant cell *** drugs enhance PARP inhibitor/cisplatin sensitivity in both intrinsically resistant organoids and cell lines with acquired ***,our study identifies a marker gene panel for HR-proficient patients and reveals a broader application of PARP inhibitor/cisplatin in cancer therapy.

关键词： drugs BRCA panel

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Complement C7 is a novel risk gene for Alzheimer's disease in Han Chinese

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National Science Review 2019年第2期6卷 257-274页

作者： Deng-Feng zhang Yu Fan min Xu Guihong Wang Dong Wang Jin Li Li-Li Kong Hejiang Zhou Rongcan Luo Rui Bi Yong wu guo-Dong Li ming Li Xiong-jian Luo Hong-yan jiang Liwen Tan Chunjiu Zhong Yiru Fang chen zhang Nengyin Sheng Tianzi jiang Yong-Gang Yao Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province Kunming Institute of ZoologyChinese Academy of Sciences Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences Kunming College of Life Science University of Chinese Academy of Sciences Center for Neurodegenerative Diseases Department of Neurology Beijing Tiantan Hospital Capital Medical University Brainnetome Center Institute of AutomationChinese Academy of Sciences National Laboratory of Pattern Recognition Institute of Automation Chinese Academy of Sciences CAS Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of Sciences department of Psychiatry the First Affiliated Hospital of Kunming Medical University Mental Health Institute of the Second Xiangya hospital Central South University department of Neurology Zhongshan Hospital Fudan University Division of Mood Disorders Shanghai Mental Health Center Shanghai Jiao Tong University School of Medicine State Key Laboratory of Genetic Resources and Evolution Kunming Institute of Zoology Chinese Academy of Sciences KIZ–CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases Kunming Institute of Zoology Chinese Academy of Sciences

Alzheimer’s disease is the most common neurodegenerative disease,and has a high level of genetic heritability and population *** this study,we performed the whole-exome sequencing of Han Chinese patients with familial and/or early-onset Alzheimer’s disease,followed by independent validation,imaging analysis and function *** identified an exome-wide significant rare missense variant rs3792646(p.K420Q)in the C7 gene in the discovery stage(P=1.09×10-6,odds ratio=7.853)and confirmed the association in different cohorts and a combined sample(1615 cases and 2832 controls,Pcombined=2.99×10-7,odds ratio=1.930).The risk allele was associated with decreased hippocampal volume and poorer working memory performance in early adulthood,thus resulting in an earlier age of disease *** of the mutant p.K420Q disturbed cell viability,immune activation and β-amyloid *** analyses showed that the mutant p.K420Q impairs the inhibitory effect of wild type C7 on the excitatory synaptic transmission in pyramidal *** findings suggested that C7 is a novel risk gene for Alzheimer’s disease in Han Chinese.

关键词： Alzheimer’s disease whole-exome sequencing C7 neuroimaging complement system

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A unique point mutation in the fibroblast growth factor 9 gene (FGF9)defines a new Multiple Synostosis Syndrome in a large Chinese family

A unique point mutation in the fibroblast growth factor 9 ge...

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中国遗传学会“发育、遗传和疾病”研讨会

作者： Xiao-lin wu~(1*) ming-min Gu~(1*) jiang-ming yang~2 Bin Cui~1 Hai-guo zhang~1 Xiao-yi Ding~3 jian-qiang Xu~3 Wen-tao Yuan~4 Zhen-yu Lu~1 qun Gu~2 wei Huang~(3,4) Zhu-gang Wang~(1,3) 1 department of Medical Genetics,Shanghai Jiao Tong university school of medicine,Shanghai 200025,People'Republic of China (PRC) 2 Qinghai Chinese Medical hospital,Xi'ning,PRC 3 Rui-jin hospital affiliated to Shanghai Jiao Tong university school of medicine,Shanghai,PRC 4Chinese National Human Genome Center at Shanghai,PRC

Multiple synostosis syndrome(SYNS)are kinds of autosomal dominant *** has been known that mutations in NOG gene can result in Multiple Synostosis Syndrome,typel(SYNS1)and mutation in GDF5 gene can cause Multiple Synostosis Syndrome,type2(SYNS2).Here,we report a five-generation family of SYNS from Qinghai Province,*** detection for NOG and GDF5 genes were both *** named the novel genetic heterogeneity of SYNS as *** carried out the genome-wide linkage analysis and localized the disease at *** showed a unique point mutation in the gene encoding fibroblast growth factor 9(FGF9).We suggest that FGF9 mutation result in a gain of function for bone growth in SYNS3.

关键词：中国遗传学会研讨会 FGF9)defines a new Multiple Synostosis Syndrome in a large Chinese family A unique point mutation in the fibroblast growth factor 9 gene

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三维打印导板辅助关节镜下微创踝关节融合术治疗晚期踝关节炎的临床效果

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中华外科杂志 2024年第6期62卷 572-580页

作者：李广翼王诚王嘉正吴承霖张解元邹剑薛剑锋苏琰梅国华施忠民马昕上海交通大学医学院附属第六人民医院骨科上海200233

目的比较三维打印导板辅助关节镜下微创踝关节融合术和传统开放式踝关节融合术治疗晚期踝关节炎的临床效果。方法本研究为回顾性队列研究。回顾性分析2018年5月至2023年2月上海交通大学医学院附属第六人民医院骨科收治的256例行踝关节... 详细信息

目的比较三维打印导板辅助关节镜下微创踝关节融合术和传统开放式踝关节融合术治疗晚期踝关节炎的临床效果。方法本研究为回顾性队列研究。回顾性分析2018年5月至2023年2月上海交通大学医学院附属第六人民医院骨科收治的256例行踝关节融合术的晚期创伤性踝关节炎患者资料。男性119例,女性137例,年龄(59.6±9.5)岁(范围:37~83岁)。其中行接骨板螺钉内固定(外侧+内侧双入路58例,单纯外侧入路117例)175例;行传统开放式前路螺钉内固定48例(传统开放组);行三维打印导板辅助关节镜下微创踝关节融合术33例(三维打印导板组)。采用倾向性评分匹配对三维打印导板组和传统开放组患者的基本资料进行1∶1匹配,卡钳值为0.02。采用独立样本t检验、Mann-Whitney U检验、Wilcoxon符号秩检验、χ^(2)检验或矫正χ^(2)检验对患者围手术期数据及随访资料进行比较。结果三维打印导板组和传统开放组各20例匹配成功,术前基本资料的差异均无统计学意义(P值均>0.05)。与传统开放组相比,三维打印导板组的手术时间更长[(88.9±5.6)min比(77.9±11.7)min;t=-2.392,P=0.022],但术中透视次数更少[(1.7±0.8)次比(5.2±1.2)次;t=10.604,P2.480,P=0.018],差异均有统计学意义。三维打印导板组的融合率为95.0%(19/20),传统开放组为85.0%(17/20),组间差异无统计学意义(χ^(2)=0.278,P=0.598);传统开放组的融合时间为(12.1±2.0)周,三维打印导板组为(11.1±1.7)周,组间差异无统计学意义(t=1.607,P=0.116)。末次随访时,三维打印导板组的美国足踝外科学会踝与后足评分为(72.6±5.5)分,传统开放组为(70.5±5.8)分,差异无统计学意义(t=-1.003,P=0.322);三维打印导板组的疼痛视觉模拟评分为[M(IQR)]1.50(1.00)分,低于传统开放组的3.00(1.00)分,差异有统计学意义(Z=-3.937,P25.0%(5/20)比5.0%(1/20),χ^(2)=1.765,P=0.184]。结论三维打印导板辅助关节镜进行踝关节融合术与传统开放手术相比,手术时间略长,但在减少术中透视次数、减轻术后疼痛和缩短住院天数方面有一定优势。

关键词：骨关节炎踝关节踝关节炎踝关节融合术关节镜导板三维打印

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Transcutaneous electroacupuncture alleviates postoperative ileus after gastrectomy: A randomized clinical trial

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World Journal of Gastrointestinal Surgery 2018年第2期10卷 13-20页

作者： Kai-Bo chen Yi-Qiao Lu jian-De chen Di-Ke Shi Zhi-Hui Huang Yi-Xiong Zheng Xiao-Li Jin Zhe-Fang Wang wei-Dong zhang Yi Huang Zhi-wei wu guo-Ping zhang Hang zhang Ying-Hao jiang Li chen department of General Surgery Second Affiliated Hospital of Zhejiang University School of MedicineHangzhou 310000Zhejiang ProvinceChina department of Obstetrics and Gynecology Women’s HospitalZhejiang University School of MedicineHangzhou 310006Zhejiang ProvinceChina Division of Gastroenterology and Hepatology Johns Hopkins University School of MedicineBaltimoreMD 21224United States department of Gastroenterology Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016Zhejiang ProvinceChina department of General Visceral and Cancer SurgeryUniversity of CologneCologne 50937Germany department of Thyroid Surgery Ningbo No.2 HospitalNingbo 315000Zhejiang ProvinceChina department of Chinese medicine Rehabilitation Second Affiliated Hospital of Zhejiang University School of MedicineHangzhou 310000Zhejiang ProvinceChina department of General Surgery First People’s Hospital of WenlingTaizhou 317500Zhejiang ProvinceChina

AIM To investigate the efficacy and safety of transcutaneouselectroacupuncture(TEA) to alleviate postoperative ileus(POI) after *** From April 2014 to February 2017, 63 gastric cancer patients were recruited from the Second affiliated hospital of zhejiang university school of medicine, Hangzhou, China. After gastrectomy, the patients were randomly allocated to the TEA(n = 33) or control(n = 30) group. The patients in the TEA group received 1 h TEA on Neiguan(ST36) and Zusanli(PC6) twice daily in the morning and afternoon until they passed flatus. The main outcomes were hours to the first flatus or bowel movement, time to nasogastric tube removal, time to liquid and semi-liquid diet, and hospital stay. The secondary outcomes included postoperative symptom assessment and *** Time to first flatus in the TEA group was significantly shorter than in the control group(73.19 ± 15.61 vs 82.82 ± 20.25 h, P = 0.038), especially for open gastrectomy(76.53 ± 14.29 vs 87.23 ± 20.75 h, P = 0.048). Bowel sounds on day 2 in the TEA group were significantly greater than in the control group(2.30 ± 2.61/min vs 1.05 ± 1.26/min, P = 0.017). Time to nasogastric tube removal in the TEA group was earlier than in the control group(4.22 ± 1.01 vs 4.97 ± 1.67 d, P = 0.049), as well as the time to liquid diet(5.0 ± 1.34 vs 5.83 ± 2.10 d, P = 0.039). hospital stay in the TEA group was significantly shorter than in the control group(8.06 ± 1.75 vs 9.40 ± 3.09 d, P = 0.041). No significant differences in postoperative symptom assessment and complications were found between the groups. There were no severe adverse events related to *** TEA accelerated bowel movements and alleviated POI after open gastrectomy and shortened hospital stay.

关键词： Transcutaneous electroacupuncture Gastrectomy Postoperative ileus

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Factors underlying the association of body mass index with serum ALT in Chinese hypertensive adults without known hepatic diseases

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Journal of zhejiang university-Science B(Biomedicine & Biotechnology) 2013年第8期14卷 743-748页

作者： yan zhang Xian-hui QIN jian-ping LI Yi-min CUI Ze-yuan LIU Zhi-gang ZHAO Jun-bo GE De-ming GUAN jian HU yan-ni WANG Fu-min zhang Xin XU Xi-ping XU Yong HUO department of Cardiology Peking University First Hospital Division of Nephrology Nanfang Hospital Southern Medical University department of Clinical Pharmacology Peking University First Hospital department of Pharmacy the First Affiliated Hospital of Academy of Military Medical Sciences of China department of Pharmacy Beijing Tiantan Hospital Capital Medical University department of Cardiology Zhongshan Hospital Fudan University department of Cardiology the First Clinical Medical College of Harbin Medical University department of Cardiology the First Affiliated Hospital of China Medical University department of Cardiology the First Affiliated Hospital of School of Medicine Xi'an Jiaotong University department of Cardiology the First Affiliated Hospital of Nanjing Medical University Guangdong Institute of Nephrology Southern Medical University

Objective： High body mass index （BMI） is considered as the most important risk factor for elevated serum alanine aminotransferase （ALT） concentration. This study examined an array of factors, including waist circumference （WC） and folate deficiency, which may mediate the association of BMI with serum ALT concentration in Chinese hypertensive adults without known hepatic diseases. Methods： A multicenter, cross-sectional study was carried out. A total of 378 patients with mild or moderate hypertension and without known hepatic diseases were recruited from five hospitals in Harbin, Shanghai, Beijing, Xi＇an, and Nanjing. Results： Of the 360 hypertensive patients with complete data in our final analysis, 13.6% had high ALT concentrations （〉40 IU/L）. Factors including BMI, WC, triglycedde level, and folate concentration were associated with ALT concentration in univariate analysis. Consistently higher preva- lence rates of elevated ALT were observed in subjects with lower folate concentrations （≥12 vs. 〈12 nmol/L, 9.9% vs. 17.8%, P=-0.03）, with higher BMI （≥28 vs. 〈28 kg/m2, 21.5% vs. 11.4%, P=-0.02） or higher WC （≥90 vs. 〈90 cm, 18.5% vs. 10.0%, P=-0.02）. However, in multivariate analysis, the association between BMI and ALT concentration disap- peared （P=-0.802 in males and 0.369 in females）, while WC in females （P〈0.001） and folate concentration （P=-0.036 in males and 0.044 in females） remained as significant predictors for ALT concentration. Conclusions： This multicenter study demonstrated that WC and low folate concentration were important factors underlying the association between BMI and ALT concentrations in Chinese hypertensive adults without known hepatic diseases.

关键词： Alanine aminotransferase (ALT) Body mass index (BMI) Waist circumference (WC) Folate

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CD 147 receptor is essential for TFF3-mediated signaling regulating colorectal cancer progression

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Signal Transduction and Targeted Therapy 2021年第8期6卷 2521-2535页

作者： Hong-Yong Cui Shi-Jie Wang Fei Song Xu cheng Gang Nan Yu Zhao Mei-Rui Qian Xi chen Jia-Yue Li Fen-Ling Liu Yu-Meng Zhu Ruo-Fei Tian Bin Wang Bin wu yang zhang Xiu-Xuan Sun ting guo Xiang-min yang Hai zhang Ling Li Jing Xu Hui-Jie Bian jian-Li jiang Zhi-Nan chen National Translational Science Center for Molecular medicine and department of Cell Biology Fourth Military Medical UniversityXi'anChina department of Urology Shenzhen Institute of Translational MedicineThe First Affiliated Hospital of Shenzhen UniversityShenzhen Second People's HospitalShenzhenChina Medical Research Institute School of MedicineWuhan UniversityWuhanChina College of Chemistry and Materials Science Northwest UniversityXi'anChina National Facility for Protein Science Shanghai Zhangjiang LabShanghai Advanced Research InstituteChinese Academy of SciencesShanghaiChina Medical Research Center Southern University of Science and Technology HospitalShenzhenChina

Major gaps in understanding the molecular mechanisms of colorectal cancer(CRC)progression and intestinal mucosal repair have hampered therapeutic development for gastrointestinal *** factor 3(TFF3)has been reported to be involved in CRC progression and intestinal mucosal repair;however,how TFF3 drives tumors to become more aggressive or metastatic and how TFF3 promotes intestinal mucosal repair are still poorly ***,we found that the upregulated TFF3 in CRC predicted a worse overall survival ***3 deficiency impaired mucosal restitution and ***147,a membrane protein,was identified as a binding partner for *** binding to CD147,TFF3 enhanced CD147-CD44s interaction,resulting in signal transducer and activator of transcription 3(STAT3)activation and prostaglandin G/H synthase 2(PTGS2)expression,which were indispensable for TFF3-induced migration,proliferation,and ***2-derived PGE2 bound to prostaglandin E2 receptor EP4 subtype(PTGER4)and contributed to TFF3-stimulated CRC *** NMR studies of the TFF3-CD147 interaction revealed the key residues critical for TFF3 binding and the induction of PTGS2 *** ability of TFF3 to enhance mucosal restitution was weakened by a PTGS2 *** of TFF3-CD147 signaling using competitive inhibitory antibodies or a PTGS2 inhibitor reduced CRC lung metastasis in *** findings bring strong evidence that CD147 is a novel receptor for TFF3 and PTGS2 signaling is critical for TFF3-induced mucosal restitution and CRC progression,which widens and deepens the understanding of the molecular function of trefoil factors.

关键词： TFF3 colorectal impaired

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